RUNX3 Inactivates Oncogenic MYC Through Disruption of MYC/MAX Complex and Subsequent Recruitment of GSK3β-FBXW7 Cascade

Overview

Journal Commun Biol

Specialty Biology

Date 2023 Jul 3

PMID 37400551

Authors

Vincent Oei

Linda Shyue Huey Chuang

Junichi Matsuo

Supriya Srivastava

Ming Teh

Yoshiaki Ito

Affiliations

Soon will be listed here.

Abstract

MYC is one of the most commonly dysregulated proto-oncogenes in cancer. MYC promotes cancer initiation and maintenance by regulating multiple biological processes, such as proliferation and stem cell function. Here, we show that developmental regulator RUNX3 targets MYC protein for rapid degradation through the glycogen synthase kinase-3 beta-F-box/WD repeat-containing protein 7 (GSK3β-FBXW7) proteolytic pathway. The evolutionarily conserved Runt domain of RUNX3 interacts directly with the basic helix-loop-helix leucine zipper of MYC, resulting in the disruption of MYC/MAX and MYC/MIZ-1 interactions, enhanced GSK3β-mediated phosphorylation of MYC protein at threonine-58 and its subsequent degradation via the ubiquitin-proteasomal pathway. We therefore uncover a previously unknown mode of MYC destabilization by RUNX3 and provide an explanation as to why RUNX3 inhibits early-stage cancer development in gastrointestinal and lung mouse cancer models.

Citing Articles

RUNX transcription factors: biological functions and implications in cancer.

Chen X, Wang L, Yang M, Zhao W, Tu J, Liu B Clin Exp Med. 2024; 24(1):50.

PMID: 38430423 PMC: 10908630. DOI: 10.1007/s10238-023-01281-0.

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